ESMO 2022 | Real-world monitoring of ctDNA reliably predicts cancer recurrence in resected stages I-III CRC

We’re still trying to figure out how to use this information. So, in our particular study, we had over 16,000 patients in our overall cohort. And then, the clinicians who had been ordering these tests were asked to submit the clinical data and be part of the investigative team. And so, when they opted into this and shared the clinical information, we were able to get a very good clinically annotated cohort of about 400 patients. And from that, we looked at a subset who had an MRD time point, or molecular residual disease time point, meaning a blood draw two to eight weeks after surgery. So then, we looked at that particular time point, which seems to be key in deciding the prognostication for patients, and we had about 150 patients that we were able to analyze. We saw 22% of our patients had detectable ctDNA, and it seemed to be worse in higher stages, which is similar to other observational studies.

And this was pretty similar in frequency to what was seen in the overall cohorts. We think we have a representative population. So, when we looked at our study, we looked specifically at issues related chemotherapy use, clinical outcomes, and especially recurrence free survival. So, we saw that of the patients who had MRD-negative, or ctDNA-negative, disease at that time point, that they did pretty good but still had a relapse rate of about 5%. So, we don’t think that being ctDNA-negative means that you’ll never have cancer occur, just that it’s highly unlikely. On the other hand, when we look at patients who are ctDNA-positive, they had a much higher recurrence rate. And that was especially true if you looked at patients that were over six months from surgery and after their adjuvant chemotherapy if used. And those patients, when they were ctDNA-positive, they had a very high recurrence rate.

So, we think that this is a very good prognostic marker, not just in the limited populations that were studied before, but now in a real world population, as well. So, that was very interesting to us. The other thing that we found interesting was looking specifically at adjuvant chemotherapy. And again, this was a small subset of our population because we have limited data at this point. But we did not actually observe a benefit from adjuvant chemotherapy in patients who were ctDNA-negative. So, in these so-called good risk patients, we’re not really seeing that same benefit from getting adjuvant chemotherapy. However, of course, we need larger numbers and additional analyses to really say if this is something that we should change treatment paradigms. But it really starts to suggest that these predictive studies, meaning studies that are actually using ctDNA to guide therapy, are very interesting because, in the end, we would like to decrease toxic therapies for patients who don’t need it and escalate therapies for patients who might need more than standard of care.